Albinism (also called achromia, achromasia, or achromatosis) is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair, and eyes due to absence or defect of an enzyme involved in the production of melanin. Certain forms of albinism are known to be due to mutations in tyrosine metabolism. Albinism results from inheritance of recessive gene alleles and is known to affect all vertebrates, including humans. There is also known an X-linked form of albinism. Patients with albinism have significant visual disability.
In oculocutaneous albinism (OCA) (despite its Latin-derived name meaning “eye-and-skin” albinism), pigment is lacking in the eyes, skin, and hair. (The equivalent mutation in non-humans also results in lack of melanin in the fur, scales, or feathers.) People with oculocutaneous albinism can have anything from no pigment at all to near normal levels of pigmentation. There are at least three general types of OCA, characterized as Type 1, Type 2 and Type 3.
Oculocutaneous albinism type 1 (OCA1) is caused by a mutation in the tyrosinase gene, and can occur in two variations. Tyrosinase converts tyrosine to dihydroxyphenylalanine (DOPA) and DOPAquinone. The first type OCA1 mutation found was identified as OCA1a, resulting in an organism that cannot develop pigment at all. The hair is usually white (often translucent) and the skin very pale. Vision in an affected individual usually ranges from 20/200 to 20/400. A second known type OCA1 mutation is identified as type OCA1b, which itself has several subtypes. This is a less severe form of albinism and some affected individuals with OCA1b can actually tan and develop pigment in the hair.
Patients with albinism experience varying degrees of vision loss associated with foveal hypoplasia, nystagmus, photophobia and/or glare sensitivity, refractive errors, and abnormal decussation of ganglion cell axons at the optic chiasm. Current treatment options for vision problems caused by albinism are limited to correction of refractive errors and amblyopia, low vision aids, and (in some cases) extraocular muscle surgery.
Another form of albinism is ocular albinism. Ocular albinism is a genetic condition that primarily affects the eyes. In ocular albinism, only the eyes lack pigment. People who have ocular albinism have generally normal skin and hair color, although their coloration is typically lighter than either parent. Many even have a normal eye appearance. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina, which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision.
Ocular albinism is characterized by severely impaired sharpness of vision (visual acuity) and problems with combining vision from both eyes to perceive depth (stereoscopic vision). Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include rapid, involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and increased sensitivity to light (photophobia). Many affected individuals also have abnormalities involving the optic nerves, which carry visual information from the eye to the brain.
Unlike some other forms of albinism, ocular albinism does not significantly affect the color of the skin and hair. People with this condition may have a somewhat lighter complexion than other members of their family, but these differences are usually minor.
Ocular albinism type 1 results from mutations in the GPR143 gene. This gene is responsible for making a protein that plays a role in pigmentation of the eyes and skin. The GPR143 gene helps control the growth of melanosomes, which are cellular structures that produce and store a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. In the retina, this pigment also plays a role in normal vision.
Most mutations in the GPR143 gene alter the size or shape of the GPR143 protein. Many of these genetic changes prevent the protein from reaching melanosomes to control their growth. In other cases, the protein reaches melanosomes normally, but mutations disrupt the protein's function. As a result of these changes, melanosomes in skin cells and the retina can grow abnormally large. Researchers are uncertain how these giant melanosomes are related to vision loss and other eye abnormalities in people with ocular albinism.
Currently, treatments for the visual impairment of oculocutaneous albinism are quite limited, and children with OCA may be left with vision approaching or reaching legal blindness. Even a modest effect on visual function (such as reduction of glare and light sensitivity) is greatly appreciated by patients.
As such, there exists a need for improving the treatment of patients, particularly for improving the vision of patients, suffering from various forms of albinism.